Caprine arthritis-encephalitis virus (CAEV) is a lentivirus related to the ovine maedi/visna and equine infectious anemia viruses and to the human lentivirus implicated in acquired immune deficiency syndrome. CAEV causes a complex inflammatory disease syndrome in domestic goats characterized principally by progressive arthritis in adults. The insidious course of CAE arthritis and the resultant pathology are markedly similar to the chronic human arthritides, particularly rheumatoid arthritis. CAE arthritis is caused by immunopathologic processes initiated by immune responses to the viral gp135 envelope glycoprotein. The progressive course of disease is maintained by persistent viral antigen expression in the presence of anti-viral immune responses. The objective of studies in this laboratory is to define the immunologic and virologic mechanisms involved in disease pathogenesis. This proposal will evaluate mechanisms that may contribute to persistent virus replication and disease, including (1) establishment of latently-infected cells in which viral gene expression is restricted and (2) emergence and selection of virus expressing antigenic variation of gp135. These studies may also be relevant to the development of protective immunization strategies for persistent lentiviral disease.